title: Major role of GABA(A)-receptor mediated tonic inhibition in propofol suppression of supraoptic magnocellular neurons.
abstract: Using slice patch clamp recording, we examined the effects of general anesthetic propofol (2,6-diisoprophlphenol) on dual modality of GABA(A) inhibition in supraoptic nucleus (SON) magnocellular neurosecretory cells (MNCs): conventional quantal synaptic transmission (IPSCs, I(phasic)) and persistent tonic form of inhibitory current (I(tonic)). Propofol (10 μM) enhanced I(tonic) as shown by an inward shift in I(holding) (16.46±2.93 pA, n=27) and RMS increase (from 3.37±0.21 pA to 4.68±0.33 pA, n=27) in SON MNCs. Propofol also prolonged the decay time of IPSCs with decreased IPSCs frequency but no significant changes in IPSCs amplitude. Overall, propofol (1-10 μM) caused much smaller increase in mean I(phasic) than mean I(tonic) at all tested concentrations. In consistent with the enhancement of GABA(A) currents, propofol attenuated ongoing firing activities of SON MNCs by ∼65% of control. Selective inhibition of I(phasic) by a GABA(A) antagonist, gabazine (1 μM), failed to block the propofol suppression of the firing activities, while inhibition of I(tonic) and I(phasic) by bicuculline (20 μM) efficiently blocked the propofol-induced neurodepression in SON MNCs. Taken together, our results showed that propofol facilitated I(tonic) with marginal increase in mean I(phasic), and this could be a mechanism reducing the intrinsic SON MNCs excitability during propofol anesthesia.
authors.affiliation: Department of Physiology, Brain Research Institute, College of Medicine, Chungnam National University, 6 Munhwa-Dong, Joong-Gu, Daejeon 301-131, Republic of Korea.
authors.forename: Ji Ae
authors.initials: JA
authors.lastname: Jeong
authors.forename: Eun Jin
authors.initials: EJ
authors.lastname: Kim
authors.forename: Ji Yoon
authors.initials: JY
authors.lastname: Jo
authors.forename: Jae Gyuk
authors.initials: JG
authors.lastname: Song
authors.forename: Kyu Seung
authors.initials: KS
authors.lastname: Lee
authors.forename: Hyun Woo
authors.initials: HW
authors.lastname: Kim
authors.forename: Sang Do
authors.initials: SD
authors.lastname: Lee
authors.forename: Byeong Hwa
authors.initials: BH
authors.lastname: Jeon
authors.forename: Jung Un
authors.initials: JU
authors.lastname: Lee
authors.forename: Jin Bong
authors.initials: JB
authors.lastname: Park
mesh_terms: D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D000818:Animals; D058787:GABA-A Receptor Antagonists / Q000494:pharmacology; D053444:Inhibitory Postsynaptic Potentials / Q000187:drug effects; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018408:Patch-Clamp Techniques; D015742:Propofol / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000378:metabolism*; D013495:Supraoptic Nucleus / Q000187:drug effects / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects
chemical_list: D018686:Anesthetics, Intravenous; D058787:GABA-A Receptor Antagonists; D011963:Receptors, GABA-A; D015742:Propofol